MISTIE-3 and MISTIE-III
Clinical Trial Details
Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III (MISTIE-III)
A phase III, randomized, case-controlled, open-label, 500-subject clinical trial of minimally invasive surgery plus rt-PA in the treatment of intracerebral hemorrhage (ICH).
MISTIE 3: At 1-year post-ICH, functional recovery was not improved when comparing the image-guided minimally invasive MISTIE procedure + alteplase to traditional medical therapy to treat medium to large intracerebral hemorrhage. It may reduce death, and more benefit was seen with a smaller residual volume.
MISTIE III: The more the volume of the ICH is reduced during surgery to treat intracerebral hemorrhage, the greater the likelihood of a good functional outcome, with ≤15 mL indicated as a threshold.
MISTIE 3: Neutral results - At 1-year post-ICH, functional recovery was not improved when comparing the image-guided minimally invasive MISTIE procedure + alteplase for 3 days to traditional medical therapy: 45% had mRS 0-3 in MISTIE patients vs 41% in medical treatment group (p=0.33). More benefit was seen with smaller residual volumes. MISTIE procedure vs medical therapy was safe at 30 days.
MISTIE lll: The more the volume of the ICH is reduced during surgery, the greater the likelihood of a good functional outcome, with a threshold of ≤15 mL. More surgeon experience was associated with lower residual volume results.
- mRS 0-3 vs 4-6 at 365 days: adjusted difference 3%, p=0.47 - primary endpoint
- 59% of surgical patients had <15 mL EOT volume – surgical goal
- eGOS score (degree of disability): MISTIE (38%) vs medical (34%)
- Safety at 30-days - Death: MISTIE 9% vs medical treatment 15%, p=0.07. Bleeding: MISTIE 2% vs medical treatment 0%. Brain infection: MISTIE 1% vs medical treatment 0%, p=0.16. Serious adverse event ≥ 1: MISTIE 30% vs medical treatment 33%.
- ICH removal and good outcome: p>0.001
- <15 mL residual hematoma volume: mRS (10%), eGOS (12%); p=0.01
- ICH removal of <15 mL = benefit: adjusted odds ratio (AOR)=1.75, p=0.030
- mRS 0-3 corelated with efficiency of clot removal: AOR=0.63/10 mL time-averaged ICH, p<0.001
- Better ICH evacuation was associated with deep ICH (OR 2.08, p=0.03) and greater site and surgeon experience (P<0.0001)
MISTIE-3 With Dan Hanley, MD and Issam Awad, MD
Bruce Ovbiagele, MD, MSc, MAS, MBA interviews Dan Hanley, MD and Issam Awad, MD, co-principal investigators of the MISTIE 3 trial about what the results suggest for treating patients with ICH.
Purpose: to compare 1-year functional recovery with minimally invasive surgery using the MISTIE procedure, a catheter-based ICH clot removal approach for stable large hematomas, to standard therapy.
Trial Design: Phase 3; n=499; 74 sites; Randomized to MISTIE + alteplase for 3 days, or standard medical therapy. 61% male; average age 61.
Primary Endpoints: blinded assessment of modified Rankin Scale (mRS) at 1 year.
|At 365 Days||MISTIE||eGOS||Standard Medical
|Clot volume reduced to ≤ 15 mL benefit||10%||12%||0.01|
|mRS @365 days adjusted 3% difference||0-3||4-6||0.47|
|eGOS score (degree of
disability) 4% difference
Results: Neutral results - At 1-year post-ICH, functional recovery was not improved when comparing the image-guided minimally invasive MISTIE procedure + alteplase for 3 days to traditional therapy. Mortality was not increased, and more benefit was seen with smaller residual volumes. Compared to medical therapy, the MISTIE procedure was safe.
Purpose: Examination of the amount of blood removal during surgery for large intracerebral hemorrhages (ICH) and better functional outcomes at one year.
Trial Design: a surgical intervention cohort of the MISTIE lll trial; n=242; measured surgical performance for the efficacy and degree of clot removal and functional outcomes (mRS 0-3) at 1 year.
Primary Endpoints: benefits (functional recovery) if surgical goal of <15 mL at end of treatment is achieved. Modified Rankin Scale (mRS) 0-3 or ≥70% volume reduction at 1 year.
|Endpoint||End-of-therapy goal <15 mL||End-of-therapy goal <15 mL||Increasing end-of-therapy size|
|mRS 0-3||AOR 1.75, p=0.030||AOR 0.76, p=0.238||Decrease in AOR (1.80-1.53) P=0.068|
|mRS 0-3 correlated with amount of clot removal AOR=0.63/10 mLtime-averaged ICH, p<0.001|
|Deep ICH had better blood removal OR 2.08, p=0.03|
|Deep ICH had better blood removal found with more experience for sites and surgeons. p<0.0001|
Results: The more the volume of the ICH is reduced during surgery, the greater the likelihood of a good functional outcome, with ≤15 mL indicated as a threshold. 59% of surgical patients had <15 mL EOT volume. More surgeon experience was associated with lower residual volume results.
ISTIE 3: Assessment of functional outcome using minimally invasive thrombectomy (image-guided catheter evacuation and thrombolysis) to achieve a residual volume of 15 ml in intracerebral hemorrhage (ICH).
MISTIE lll: evaluation of amount of blood removed during surgery for ICH and functional outcome.
Trial design: phase 3, open-label, image-guided randomization, blinded, case-controlled trial. N=499; surgical cohort 242 patients; 78 sites; Patients randomized to MISTIE + 1.0 mg alteplase q8h up to 9 doses, or standard medical therapy.
Patients: 61% male; average age 61.
Primary endpoints: good functional outcome measured by modified Rankin Scale (mRS) in intention to treat. (mRS measures degree of disability or dependence in daily activities.)
- MISTIE 3 – modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 1 year after ICH = good functional outcome
- MISTIE lll – surgical: functional recovery (modified Rankin Scale (mRS) 0-3 at 1 year after ICH) if ICH blood volume at the end of surgery of <15 mL or ≥70% volume reduction is achieved.
Other Endpoints: MISTIE lll – surgical outcomes
- 30-day serious adverse events: all-cause mortality, brain bleeding, brain infection
Primary endpoints: (mRS = ICH (functional recovery - degree of disability or dependence in the daily activities)
- MISTIE 3: modified Rankin Scale (mRS) score 0-3 vs. 4-6 at 1 year after
- MISTIE III: benefits (functional recovery) if surgical goal of <15 mL at end of treatment is achieved. Modified Rankin Scale (mRS) 0-3 or ≥70% volume reduction at 1 year after ICH.
Secondary endpoints: MISTIE III
- Extended Glasgow Outcome Scale (eGOS) score upper good recovery (UGR) through upper severe disability (US) vs. lower severe disability (LS) through death at 365 days after ICH.
- All-cause mortality longitudinally from ICH to 365 days
- Clot removal (amount of residual blood)
- Patient disposition
Other endpoints: MISTIE III
30-day mortality and safety: all-cause mortality, brain bleeding, infection, SAE’s
- Presented by Issam A. Awad (MISTIE III) and Daniel F Hanley (PI, MISTIE 3) at International Stroke Conference 2019, Honolulu, Hawaii
- clinicaltrials.gov: NCT01827046
- MISTIE 3 Abstract
- MISTIE 3 Presentation Slides (PDF)
- MISTIE III Abstract
- MISTIE III Presentation Slides (PDF)
- Minimally Invasive Surgery for Intracerebral Hemorrhage: An Updated Meta-Analysis of Randomized Controlled Trials, Stroke 2018
Intracerebral hemorrhage, ICH, brain hemorrhage, minimally invasive surgery, rt-PA
Related Clinical Topics
Stroke, intracerebral hemorrhage, rehabilitation, functional outcome, intracerebral hemorrhage, modified Rankin Scale, tissue plasminogen activator